Eröffnungssymposium des Amyloidosezentrums Heidelberg 02 05 0902.05.09

Amyloid: Der fokussierte Blicky

Die Sicht des PathologenPh. A. Schnabel1, B. Helmke1, A. Kristen2, T. Longerich1, N. Gassler1, J. Moyers1, T.J. Dengler2, P. Schirmacher1

1P th l i h I tit t 2M di i i h Kli ik Abt K di l i1Pathologisches Institut, 2Medizinische Klinik, Abt. Kardiologie und Pulmologie, Universitäts-Klinikum Heidelberg

Distribution patterns of amyloid Distribution patterns of amyloid in the myocardium

Findings in endomycardial biopsies

Findings in explanted hearts

Pathophysiology

W k iWork in progress Virtual microscopyV tua c oscopy

Subendocardial distributionSubendocardial distributionE-28681/02 A2; HE (5x)E-28681/02 A2; HE (5x)

Subendocardial distributionSubendocardial distributionE-28681/02 A3; Kongo red (5x)E-28681/02 A3; Kongo red (5x)

Endomysial distributionEndomysial distributionyE-28681/02 A; HE (5x)

yE-28681/02 A; HE (5x)

Endomysial distributionEndomysial distributionyE-28681/02 A1; Kongo red (5x)

yE-28681/02 A1; Kongo red (5x)

(Peri-) Vascular distribution(Peri-) Vascular distribution( )E-11833/01 A; HE (10x)

( )E-11833/01 A; HE (10x)

(Peri-) Vascular distribution(Peri-) Vascular distributionE-11833/01A1; Kongo red (10x)E-11833/01A1; Kongo red (10x)

(Micro-) Nodular distribution(Micro-) Nodular distributionE-1960/01 A; HE (10x)E-1960/01 A; HE (10x)

(Micro-) Nodular distribution(Micro-) Nodular distributionE-1960/01 A1; Kongo red (10x)E-1960/01 A1; Kongo red (10x)

Distribution of amyloid in endomyocardial biopsies

Diffuse endomysial: 24 / 27

(Peri-) / Vascular: 20 / 27

(Sub-) Endocardial: 17 / 27

(Mi ) N d lä 11 / 27(Micro-) Nodulär: 11 / 27

Endomysial > Vascular > Endocardial > Nodular

Distribution of amyloid in an explanted heart y pE-2434/05: A Macro, B Kongo red

Distribution of amyloid in an explanted heartE 2434/05 A M B F K d B E i diE-2434/05: A Macro, B – F Kongo red, B Epimyocardium,

C – E Mural myocardium, F Endomyocardium

Predominant distribution patterns of amyloid in explanted heartsp

Diffuse endomysial: 3 / 4

(Peri-) Vascular: 1 / 4

(Sub-) Endocardial: 0 / 4

Perimysial: 0 / 4

(Micro-) Nodular: 0 / 4

Endomysial >> Vascular > Endocardial = Perimysial = Nodular

Pathophysiology: Endomysium E 11674/00 A; HE (10x)

Pathophysiology: Endomysium E 11674/00 A; HE (10x)E-11674/00 A; HE (10x)E-11674/00 A; HE (10x)

Pathophysiology: Endomysium Pathophysiology: Endomysium p y gy yE-11833/01A1; Kongo red (10x)

p y gy yE-11833/01A1; Kongo red (10x)

Pathophysiology of amyloid distribution patterns

Diffuse endomysial: Restriction, altered micro-environment &electrophysiology, oxidative stress, (ischemia)

(Peri-) Vascular: Ischemia, fibrosis, altered mechanics

(Sub-) / endocardial: Restriction, (ischemia)

P i i l Alt d h i t i ti (i h i )Perimysial: Altered mechanics, restriction, (ischemia)

(Micro-) Nodular: Lokal mechanics, conduction disturbances( ) ,

Endomysial = Vascular >> Perimysial = Endocardial >> Nodular

Work in progress: Amyloid in endomyocardial biopsiesAmyloid in endomyocardial biopsies

i b d l id i Differences between AL und ATTR amyloidosis ? Predominant distribution patterns ?p Correlations with clinical data ? C l ti ith t ? Correlations with outcome ? Correlation with distribution patterns in explanted hearts ?

Work in progress: Amyloid in endomyocardial biopsiesAmyloid in endomyocardial biopsies

Amyloid Grade Subendoc Endomys Perivasc Vascular MicronodAmyloid Grade Subendoc. Endomys. Perivasc. Vascular Micronod.AL 0 8 3 12 5 17n=30 1 8 8 2 10 6

2 10 8 8 5 53 4 11 7 9 2

ATTR 0 2 0 4 7 6n=12 1 7 2 7 2 2

2 3 3 0 1 23 0 7 0 1 2

Conclusions

To investigate the amyloid distribution in the myocardium, exact and reproducable definitions aremyocardium, exact and reproducable definitions are necessary.

In explanted hearts we can test how representative In explanted hearts we can test how representative biopsy results are and which pathophysiological consequences can be derivedconsequences can be derived.

Correlations between morphological, clinical and radiological results can be found.

Summary

The distribution of amyloid can be evaluated in endomycardial biopsies (or explanted hearts) asendomycardial biopsies (or explanted hearts) as endomysial, (peri-) vascular, subendocardial, (perimysial) and nodular.(perimysial) and nodular.

The predominant distribution pattern of amyloid can be determined precisely in explanted hearts.be determined precisely in explanted hearts.

Pathophysiologically the endomysial and the vascular distribution patterns are most significant.distribution patterns are most significant.

Systematic investigations of the amyloid distribution patterns in relation to functional and prognostic datapatterns in relation to functional and prognostic data may contribute to clarify special aspects of the pathophysiology of myocardial amyloidosis and finally thpathophysiology of myocardial amyloidosis and finally thindication for heart transplantation.

E-2624/05: A Makro, B Kongorot, g

E-2624/05: A Makro, B – F Kongorot, B E d k d C E M l M k d FEndomyokard, C – E Murales Myokard, F

Epimyokard

Amyloidverteilung in Explantaten/ bei Autopsie

Diffus interstitiell (endomysial): 4 / 4

Perimysial: 4 / 4

(Peri-) / Vaskulär: 4 / 4

(S b ) E d k di l 4 / 4(Sub-) Endokardial: 4 / 4

(Mikro-) Nodulär: 2 / 4 ( )

Interstitiell = Vaskulär = Endokardial > Nodulär